Life extension by a factor of 10

Experiments extending the lives of mice up to about 35% have been reported, and that is about it.  However, last year an experiment was reported that extended the life span of baker’s yeast by a factor of 10.  Certain genes and genetic pathways involved in longevity of primitive species like yeast are conserved by evolution in higher species including humans.  “Genes that modulate aging have been conserved not only in sequence, but also in function, over a billion years of evolution(ref).”  Studies of longevity-promoting genetic interventions are relatively easy in yeast because its life span is very short, and the hope is that insights can be realized through such studies that can eventually be applied to higher species including our own.    

The latest research involved ”knocking out two genes, known as RAS2 and SCH9, which promote ageing in yeast and cancer in humans, and putting the microbes on a diet low in calories(ref).”  The researchers reported “The deletion of both RAS2 and the Akt and S6 kinase homolog SCH9 in combination with calorie restriction caused a remarkable 10-fold life span extension, which, surprisingly, was only partially reversed by the lack of Rim15. These results indicate that the Ras/cAMP/PKA/Rim15/Msn2/4 and the Tor/Sch9/Rim15/Gis1 pathways are major mediators of the calorie restriction-dependent stress resistance and life span extension, although additional mediators are involved. Notably, the anti-aging effect caused by the inactivation of both pathways is much more potent than that caused by CR.” — “Our study also showed that by combining the genetic manipulation and calorie restriction intervention, yeast can reach a life span ten times that of those grown under standard conditions. This extreme longevity requires Rim15 and also depends on other yet-to-be identified mechanisms. Our findings provided new leads that may help to elucidate the mechanisms underlying the anti-aging effect of calorie restriction in mammals(ref).”    

There is a long history of longevity-related experiments on yeast.  Back in 2005 some of the same researchers looked at the role of SIR2 in aging in yeast.  “Rather than adding copies of SIR2 to yeast, Longo’s research group deleted the gene altogether. –The result was a dramatically extended life span – up to six times longer than normal – when the SIR2 deletion was combined with caloric restriction and/or a mutation in one or two genes, RAS2 and SCH9, that control the storage of nutrients and resistance to cell damage. — Human cells with reduced SIR2 activity also appear to confirm that SIR2 has a pro-aging effect, Longo said, although those results are not included in the Cell paper(ref).”  

A 10-fold increase in longevity in humans would bring our average life spans up to about 800 years, more than enough to satisfy any contemporary anti-aging zealot.   But, will the life-extending interventions used on the yeast also work for more advanced species?  My answer is that the knowledge gained in the yeast experiments has been valuable though the anti-aging interventions used on yeast may not work or be inappropriate.  I wrote about one of the two pathways involved in the cited experiment in an earlier blog post Longevity genes, mTOR and lifespan.  I wrote that “With respect to humans, much of the machinery of TOR signaling found in more primitive species is conserved.”  “The longevity function of SIR2 is conserved in at least one multicellular organism, Caenorhabditis elegans(ref)” and SIR1 appears to play a similar role in mammals.  SIR2 and its mammalian  counterpart SIR1 are involved in the calorie-restriction anti-aging pathway and have been the subject of much recent research(ref)(ref)(ref).  

The cited yeast research studies are interesting because they are  based on simultaneously altering two longevity-related genetic pathways to achieve extraordinary longevity, something not yet systematically studied in higher animals.   So the yeast research might ultimately prove to be very valuable for us.